WHO guidelines for antimicrobial treatment in children admitted to hospital in an area of intense Plasmodium falciparum transmission: prospective study

Abstract

Objectives: To assess the performance of WHO's "Guidelines for care at the first-referral level in developing countries" in an area of intense malaria transmission and identify bacterial infections in children with and without malaria.

Design: Prospective study.

Setting: District hospital in Muheza, northeast Tanzania.

Participants: Children aged 2 months to 13 years admitted to hospital for febrile illness.

Main outcome measures: Sensitivity and specificity of WHO guidelines in diagnosing invasive bacterial disease; susceptibility of isolated organisms to recommended antimicrobials.

Results: Over one year, 3639 children were enrolled and 184 (5.1%) died; 2195 (60.3%) were blood slide positive for Plasmodium falciparum, 341 (9.4%) had invasive bacterial disease, and 142 (3.9%) were seropositive for HIV. The prevalence of invasive bacterial disease was lower in slide positive children (100/2195, 4.6%) than in slide negative children (241/1444, 16.7%). Non-typhi Salmonella was the most frequently isolated organism (52/100 (52%) of organisms in slide positive children and 108/241 (45%) in slide negative children). Mortality among children with invasive bacterial disease was significantly higher (58/341, 17%) than in children without invasive bacterial disease (126/3298, 3.8%) (P<0.001), and this was true regardless of the presence of P falciparum parasitaemia. The sensitivity and specificity of WHO criteria in identifying invasive bacterial disease in slide positive children were 60.0% (95% confidence interval 58.0% to 62.1%) and 53.5% (51.4% to 55.6%), compared with 70.5% (68.2% to 72.9%) and 48.1% (45.6% to 50.7%) in slide negative children. In children with WHO criteria for invasive bacterial disease, only 99/211(47%) of isolated organisms were susceptible to the first recommended antimicrobial agent.

Conclusions: In an area exposed to high transmission of malaria, current WHO guidelines failed to identify almost a third of children with invasive bacterial disease, and more than half of the organisms isolated were not susceptible to currently recommended antimicrobials. Improved diagnosis and treatment of invasive bacterial disease are needed to reduce childhood mortality.

Fig 1 Admissions, deaths, inclusions, and exclusions during study. 2383/3639 (65.5%) had an axillary temperature ≥37.5 on admission, 1234/3639 (33.9%) were afebrile with a history of fever, and 22/3639 (0.6%) gave a history of fever with no temperature recorded

Fig 2 Numbers and deaths of children infected with P falciparum by blood slide, invasive bacterial disease (IBD), or HIV. Areas in Venn diagram approximately to scale. *IBD consisted of 336 children with a positive blood culture, of whom 20 also had a positive cerebrospinal fluid (CSF) culture, and an additional five with a pathogenic organism isolated from CSF and a negative or contaminated blood culture. †Blood cultures classified as negative included 251 (6.9%) from which contaminant organisms only were cultured. ‡Three negative HIV results were based on Capillus testing only (negative predictive value 99.5%, detail not shown); all other HIV results were based on at least two concordant test results

Fig 3 Proportion of organisms isolated from children with invasive bacterial disease by P falciparum infection status. RDT=rapid diagnostic test